Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma

This study has been terminated.
(The unpromising experience of the French group with topotecan given at a dosage of 0.4 mg/m2/day over 30 mins w/in 1 hr of radiation (Cancer 2005; 104: 2792).)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00107471
First received: April 5, 2005
Last updated: December 9, 2013
Last verified: December 2013

April 5, 2005
December 9, 2013
October 2005
October 2007   (final data collection date for primary outcome measure)
Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause) [ Time Frame: From date of enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death or until last contact if none of these events occur, assessed up to 3 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00107471 on ClinicalTrials.gov Archive Site
Time to death [ Time Frame: From the time of study entry to the first occurrence of death by any cause ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma
A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Topotecan may make tumor cells more sensitive to radiation therapy . Giving topotecan and G-CSF together with radiation therapy may be an effective treatment for brain stem glioma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of topotecan when given together with G-CSF and radiation therapy and to see how well they work in treating young patients with newly diagnosed brain stem glioma.

OBJECTIVES:

Primary

  • Determine the feasibility of escalating the dose of topotecan when administered with filgrastim (G-CSF) and radiotherapy, in terms of increasing the topotecan dose 25-50% above the maximum tolerated dose (MTD) determined in a prior phase I study, in young patients with newly diagnosed malignant intrinsic pontine brain stem glioma. (Phase I)
  • Determine the dose-limiting toxic effects of topotecan in these patients. (Phase I)
  • Determine the 1-year event-free survival and overall survival of patients treated with this regimen (at the MTD of topotecan determined in phase I). (Phase II)
  • Determine the toxicity of this regimen in these patients. (Phase II)

Secondary

  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study of topotecan followed by a phase II study.

  • Phase I: Patients receive topotecan IV over 30 minutes followed by radiotherapy once daily, 5 days a week for 6-7 weeks. During chemoradiotherapy, patients also receive filgrastim (G-CSF) IV or subcutaneously daily, if needed, until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 out of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive topotecan (at the MTD determined in phase I ), G-CSF, and radiotherapy as in phase I.

After completion of study treatment, patients are followed within 2 weeks, every 3 months for 1.5 years, every 6 months for 1.5 years, and then annually until disease relapse.

PROJECTED ACCRUAL: A total of 3-72 patients (3-12 for phase I and 60 for phase II) will be accrued for this study within approximately 3 years.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brain Tumors
  • Central Nervous System Tumors
  • Biological: filgrastim
    Given PO
    Other Names:
    • Granulocyte Colony-Stimulating Factor
    • r-metHuG-CSF
    • G-CSF
    • Neupogen
    • NSC #614629
  • Drug: topotecan hydrochloride
    Given IV
    Other Names:
    • SKF-104864
    • Hycamtin
    • NSC #609699
  • Radiation: radiation therapy
    Other Names:
    • Conformal therapy or Intensity modulated radiation therapy (IMRT) may be
    • used.
  • Experimental: Dose Level I (0.5 mg/m^2)
    Radiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n)
    Interventions:
    • Biological: filgrastim
    • Drug: topotecan hydrochloride
    • Radiation: radiation therapy
  • Experimental: Dose Level 2 (0.6 mg/m^2)
    Radiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n.)
    Interventions:
    • Biological: filgrastim
    • Drug: topotecan hydrochloride
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
7
Not Provided
October 2007   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of intrinsic pontine brain stem glioma within the past 30 days

    • Histologic confirmation not required provided the tumor has a pontine epicenter AND exhibits diffuse (rather than focal) involvement of ≥ 2/3 of the pons with or without extension to the adjacent medulla or midbrain* NOTE: *Brain stem tumors that do not meet these criteria must be histologically confirmed as grade III or IV malignant glioma
  • Measurable disease by radiographic imaging

    • Post-operative MRI required within the past 30 days if patient had a biopsy or surgical resection
  • No disseminated disease
  • No neurofibromatosis type 1

PATIENT CHARACTERISTICS:

Age

  • 3 to 21 at diagnosis

Performance status

  • Lansky 50-100% OR
  • Karnofsky 50-100%

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 2.5 times ULN

Renal

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
  • Creatinine based on age as follows:

    • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
    • No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
    • No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
    • No greater than 1.5 mg/dL (for patients over 15 years of age)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Not severely somnolent or comatose

    • Central cortical neurotoxicity scale < grade 3

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunomodulating agents

Chemotherapy

  • No other concurrent anticancer chemotherapy

Endocrine therapy

  • Concurrent corticosteroids allowed for neurological deficits related to the tumor

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics
  • Prior biopsy or surgical resection for malignant brain stem glioma allowed

Other

  • No other prior therapy for malignant brain stem glioma
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Switzerland
 
NCT00107471
ACNS0224, CDR0000417842, COG-ACNS0224
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Patricia L. Robertson, MD University of Michigan Cancer Center
Study Chair: Richard A. Axtell, MD Helen DeVos Children's Hospital at Spectrum Health
Children's Oncology Group
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP